About 25% of women of childbearing age carry GBS in their rectum or vagina. Half of their newborns acquire GBS at birth; 98% are said to be asymptomatic. Phospholipids from group B streptococcal (GBS) cell wall cause pulmonary hypertension in experimental animals. When exposed to penicillin, Streptococcus mutans release phospholipids immediately. We hypothesize that newborns colonized with GBS receive bacterial phospholipids leading to pulmonary hypertension and respiratory distress, especially in newborns of penicillin-treated mothers. Analysis of data from 1,610 colonized newborns of >32 weeks gestation without early-onset disease showed that 8.8% had signs of respiratory distress within 48 hours after birth. This effect was enhanced by penicillin use during labor. Our findings support the association of neonatal respiratory distress with asymptomatic GBS colonization and with penicillin use during labor. A prospective study to relate the levels of serum bacterial phospholipids to the occurrence of respiratory distress in newborns of mothers colonized by GBS, and the effects of penicillin use during labor on the occurrence of respiratory distress is underway. Assay to measure bacterial phospholipids in biological specimens in mothers and newborns are being developed in collaboration with Dr. alfred Yergey at NICHD.